de Jong S C, Stehouwer C D, van den Berg M, Geurts T W, Bouter L M, Rauwerda J A
Institute for Cardiovascular Research, Vrije Universiteit, Amsterdam, The Netherlands.
J Intern Med. 1999 Jul;246(1):87-96. doi: 10.1046/j.1365-2796.1999.00541.x.
Mild hyperhomocysteinaemia (HHC), fasting or after methionine loading, is associated with an increased risk and severity of atherosclerotic vascular disease. Post-methionine and fasting HHC are responsive to treatment with vitamin B, and folic acid. We performed a prospective cohort study amongst normohomocysteinaemic and vitamin-treated (vitamin B6, 250 mg plus folic acid, 5 mg daily) hyperhomocysteinaemic patients with premature peripheral arterial occlusive disease and assessed the incidence of cardiovascular events.
We studied 273 consecutive patients with clinically manifest peripheral arterial occlusive disease with onset before the age of 56, 79 (28.9%) of whom had postmethionine HHC. Follow-up was obtained in 232 (85'%o) patients. At baseline, 70 (30')/) were hyperhomocysteinaemic after methionine loading and started treatment with vitamin B, and folic acid; 162 (70%) were normohomocysteinaemic (reference group).
During the follow-up period (median 20, range 1-63 months), 48 (29.6%) and 23 (32.9%) of the normo- and the hyperhomocysteinaemic patients, respectively, had a new cardiovascular event. Most (75%) involved the peripheral arterial system. The crude incidence rate for any cardiovascular event was 0.16 (95% CI, 0.12-0.21) per person per year in the normohomocysteinaemic and 0.16 (95% CI, 0.09-0.22) per person per year in the hyperhomocysteinaemic group. Multivariate Cox regression analyses showed that higher plasma homocysteine levels were associated with an increased risk of new cardiovascular events in the normohomocysteinaemic patients (relative risk [RR] per 1 micromol L(-1), 1.17 [CI, 1.05-1.30] for fasting and 1.06 [CI, 1.01-1.12] for postmethionine levels), but not in the hyperhomocysteinaemic (vitamin-treated) patients. The adjusted RR for new cardiovascular events in the hyper- as compared to the normohomocysteinaemic patients was 0.76 (CI, 0.33-1.74).
These data are consistent with a protective effect of treatment with vitamin B6 and folic acid in patients with premature peripheral arterial occlusive disease and postmethionine HHC. Double-blind randomized trials are necessary to confirm this.
空腹或蛋氨酸负荷后轻度高同型半胱氨酸血症（HHC）与动脉粥样硬化性血管疾病风险及严重程度增加相关。蛋氨酸负荷后及空腹HHC对维生素B和叶酸治疗有反应。我们对正常同型半胱氨酸血症患者以及接受维生素治疗（每日250毫克维生素B6加5毫克叶酸）的高同型半胱氨酸血症且患有外周动脉闭塞性疾病的患者进行了一项前瞻性队列研究，并评估了心血管事件的发生率。
我们研究了273例临床诊断为外周动脉闭塞性疾病且发病年龄在56岁之前的连续患者，其中79例（28.9%）有蛋氨酸负荷后HHC。232例（85%）患者获得随访。基线时，70例（30%）蛋氨酸负荷后高同型半胱氨酸血症患者开始接受维生素B和叶酸治疗；162例（70%）为正常同型半胱氨酸血症患者（参照组）。
在随访期间（中位时间20个月，范围1 - 63个月），正常同型半胱氨酸血症患者和高同型半胱氨酸血症患者中分别有48例（29.6%）和23例（32.9%）发生了新的心血管事件。大多数（75%）涉及外周动脉系统。正常同型半胱氨酸血症患者中任何心血管事件的粗发病率为每人每年0.16（95%CI，0.12 - 0.21），高同型半胱氨酸血症组为每人每年0.16（95%CI，0.09 - 0.22）。多变量Cox回归分析显示，在正常同型半胱氨酸血症患者中，较高的血浆同型半胱氨酸水平与新的心血管事件风险增加相关（空腹时每1微摩尔/升相对风险[RR]为1.17[CI，1.0‘5 - 1.30]，蛋氨酸负荷后水平为1.06[CI，1.01 - 1.12]），但在高同型半胱氨酸血症（接受维生素治疗）患者中并非如此。与正常同型半胱氨酸血症患者相比，高同型半胱氨酸血症患者发生新的心血管事件的校正RR为0.76（CI，0.33 - 1.74）。
这些数据与维生素B6和叶酸治疗对患有外周动脉闭塞性疾病及蛋氨酸负荷后HHC患者有保护作用相一致。需要进行双盲随机试验来证实这一点。
